This invention relates to the immune system and, more specifically, to methods of modifying pathological immune responses in diabetes.
Higher organisms are characterized by an immune system which protects them against invasion by potentially deleterious substances or microorganisms. When a substance, termed an antigen, enters the body and is recognized as foreign the immune system mounts both an antibody-mediated response and a cell-mediated response. Cells of the immune system termed B lymphocytes, or B cells, produce antibodies that specifically recognize and bind to the foreign substance. Other lymphocytes termed T lymphocytes, or T cells, both effect and regulate the cell-mediated response, resulting eventually in the elimination of the antigen.
A variety of T cells are involved in the cell-mediated response. Some induce particular B cell clones to proliferate and produce antibodies specific for the antigen. Others recognize and destroy cells presenting foreign antigens on their surfaces. Certain T cells regulate the response by either stimulating or suppressing other cells.
While the normal immune system is closely regulated, aberrations of the response are not uncommon. In some instances, the immune system functions inappropriately and reacts to a component of the host as if it were, in fact, foreign. Such a response results in an autoimmune disease, in which the host's immune system attacks the host's own tissue. T cells, as the primary regulators of the immune system, directly or indirectly effect such autoimmune pathologies. T cells have on their surface proteins known as T cell receptors (TCR) which mediate the recognition of and activity by antigen.
Diabetes can be an autoimmune disease in which the immune system attacks critical cells of the pancreas interfering normal regulation. Insulin-dependent diabetes mellitus (IDDM), also known as type I or juvenile onset diabetes, is one such autoimmune disease which can have devastating results. While the primary effect of the disease can be controlled by administration of the insulin, secondary affects of the disease and such effects of the treatment reduce both the length and quality of life. It is estimated that there are more than a million IDDM patients in the United States alone.
A need exists for improved and effective means of curing or ameliorating diabetes. Such a treatment should ideally control the inappropriate T cell response, rather than merely reducing the symptoms. The present invention satisfies this need and provides related advantages as well.